We have investigated the specificities of antibrain antibodies in the sera of patients with senile dementia of the Alzheimer's type (SDAT). Using indirect immunofluorescence, we observed a vascular pattern of staining in 6 of 16 sera from patients with typical SDAT. None of 14 sera from age matched controls demonstrated this pattern of staining. The vascular pattern of staining seen with SDAT sera was identical to the immunofluorescent staining of brain by a monoclonal antibody to vascular basement membrane heparan sulfate proteoglycan. Immunoabsorption of SDAT sera with purified vascular proteoglycan abolished the staining of brain vessels. Using an enzyme linked immunoassay, 3 of the 6 vascular-reactive SDAT sera, and none of the 24 sera from aged controls, were shown to contain antibodies to purified vascular heparan sulfate proteoglycan. Proteoglycans play an important role in the barrier function of the blood-brain barrier. Autoimmune injury to the blood-brain barrier by antivascular antibody may play a role in the pathogenesis of dementia by permitting the passage of injurious substances into the brain.